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UV decreases Multiple Sclerosis via cis-urocanic acid (and via vitamin D) – June 2013

Modulation of multiple sclerosis by sunlight exposure: Role of cis-urocanic acid

Jorge Correale jcorreale at fleni.org.ar , Mauricio F. Farez
Received 16 March 2013; published online 24 June 2013.

The role of cis-urocanic acid (UCA) as a UV-mediated immunomodulator in MS patients was investigated. Plasma levels of cis-UCA were significantly lower in MS patients compared to controls. Stimulation of MBP- and MOG-specific T cells in the presence of cis-UCA, significantly increased IL-10, and inhibited IFN-γ production. PBMCs cultured in the presence of cis-UCA increased CD4+CD25+FoxP3+ regulatory T cell percentages. Dendritic cells cultured in the presence of cis-UCA significantly reduced Ag presentation capacity. Finally, cis-UCA activated the 5-HT2A receptor, inducing the increase in phosphorylated forms of ERK 1/2 and JNK2. Thus, in addition to vitamin D, cis-UCA also appears to be an additional UV-mediated immunomodulator.

Highlights (by publisher)

  • Relapsing remitting MS patients had significantly lower levels of cis-UCA.
  • cis-UCA increased IL-10 secretion and inhibited IFN-γ production by T cells.
  • cis-UCA increased the number of CD4+CD25+FoxP3+ regulatory T cells.
  • cis-UCA reduced Ag presentation capacity by dendritic cells.

Comments by VitaminDWiki

  1. This may explain why UV appears to be more important than vitamin D in treating MS
  2. This may explain why people believe that you should not take a shower after being in the sun
    urocanic acid is in the sweat, vs vitamin D is below the surface of the skin

See also VitaminDWiki

See also web

Jorge Correale 1 and Mauricio Farez 2 [same authors as the study at the top of this page]
1 Neurology Dr Raul Carrea Institute for Neurological Research Buenos Aires Argentina
2 Dr Raúl Carrea Institute for Neurological Research Buenos Aires Argentina

Objective: To study the role of cis-urocanic acid (UCA) in MS pathogenesis.

Background UCA is a major absorber of UV radiation in the skin. Formed as a trans-isomer from histidine in the upper epidermis, it converts to a systemically-distributed cis-isomer on exposure to sunlight, conferring immunosuppression.

Design/Methods: Ninety-two patients with relapsing remitting MS were examined, fifty-eight patients in remission and 32 during exacerbations. Forty age and gender-matched healthy subjects served as controls. Trans-, and cis-UCA plasma levels were measured by HPLC. MBP- and MOG peptide-specific T cell lines were stimulated with cognate antigens (Ags) in presence and in absence of cis-UCA, whereupon IL-4, IL-10, IL-6, IL-8, IL-17, TGF-β, TNF-α, IFN-{gamma}, and PGE2 were measured using ELISA. CD4+CD25+FoxP3+ regulatory T cells were assessed using flow cytometry.

Results: Plasma levels of cis-UCA were significantly lower in MS patients compared to controls (p= 0.001).
In contrast, no differences in plasma trans-UCA levels were found between groups, nor was any association found between disease activity and plasma cis-UCA levels.
Stimulation of MBP- and MOG-specific T cells with specific Ags in the presence of cis-UCA significantly increased IL-10 and PGE2 secretion, and inhibited IFN-{gamma} production. No effect was observed on the secretion of the other cytokines investigated. Moreover, PBMCs cultured in the presence of cis-UCA increased CD4+CD25+FoxP3+ regulatory T cell percentages 3 to 12-fold. Finally, dendritic cells cultured in the presence of cis-UCA significantly reduced their Ags presentation capacity, when proliferation and cytokines secretion were measured as read-outs of T cell activation.

Conclusions: In addition to Vitamin D, cis-UCA represents an additional UV-mediated immunomodulator, which may help explain the increased prevalence of MS observed at higher latitudes.

Disclosure: Dr. Correale has received personal compensation for activities with Merck Serono Argentina, Biogen Idec, Novartis, and from Teva Neuroscience as a speaker. Dr. Farez has nothing to disclose.


urocanic acid action spectra overlaps that of Vitamin D

Image

Vitamin D spectra is the black dotted line
in wiki page and PDF with same title

Attached files

ID Name Comment Uploaded Size Downloads
2662 Cis-urocanic acide immune.pdf admin 28 Jun, 2013 20:43 1.02 Mb 628
2657 trans-urocanic acid spectra.jpg admin 27 Jun, 2013 14:46 30.11 Kb 1610
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